Short term effect of transarterial chemoembolization (TACE) on microsomal liver function by means of 13C-methacetin breath test (MBT) in patients with hepatocellular carcinoma (HCC)

Background: Chemoembolization is a frequently applied therapeutic modality for un-resectable HCC. Transcatheter intraarterial injection of cytotoxic agents and embolization of tumor feeding arteries induce a cytotoxic and ischemic tissue effect. The MBT is a feasible non-invasive function test for the assessment of hepatic functional reserve, overall prognosis and complications in patients with chronic liver diseases. Aims: To assess in a pilot study prospectively the short term effect of conventional TACE on hepatic functional reserve by MBT and on static functional and inflammatory parameters.

Methods: 14 male patients with liver cirrhosis of different etiologies and unresectable HCC (all BCLC B and Child class A, age 65.3 ± 3.1 y., BMI 27.9 ± 1.2 kg/m², MELD 10.2 ± 0.8) were studied. Each patient received 75 mg of ¹³C-methacetin in 100 ml of water before (d₀), 24h (d₁) and 72h (d₃) after conventional TACE therapy. The ¹³C/¹²C ratio in breath was determined over 60 min in 10 min intervals by infrared spectroscopy, as delta over baseline (DOB [‰]) and was expressed as maximal ¹³C/¹²C ratio (DOB_max) and calculated percentage dose rate (PDR_max). In addition, static liver function and inflammatory markers were assessed on each study day.

Results: TACE induced a sustained decrease in microsomal liver function (PDR_max) 24h and 72h following therapy (p = 0.08; d₀ vs d₃), which was most pronounced in HCC patients with a PDR_max> 5%/h (n = 8) and lower MELD values (9.3 vs. 11.5) at d₀ (p = 0.02 d₀ vs. d₁ and p = 0.04 d₀vs d₃). Static liver function test remained unchanged (for MELD; p = 0.2 – 0.7 d₀ vs d₁, d₃) and inflammatory markers increased (for WBC (10³/µl), PCT (ng/ml), CRP (mg/dl): p = 0.02, p = 0.04, p = 0.7 d₀ vs. d₁; p = 0.003, p = 0.005, p < 0.001 d₀ vs. d₃). The increase of inflammatory markers was not associated with MBT results.

Conclusions: In this pilot study a reduction in functional hepatic reserve induced by TACE is reflected by a sustained decrease in ¹³C-methacetin metabolism over 72h whereas static liver function test remained unchanged. The postprocedural inflammatory response was not associated with the observed decrease in liver function. The MBT might therefore be helpful in the quantification of postprocedural liver function and prediction of decompensation.